Gout Risk Has Genetic Component

A large-scale study shows genes and environment have different effects in men and women.

12/12/2013 | By Jennifer Davis

But it’s not all genetics; environment and lifestyle factors such as diet, alcohol consumption and the use of certain medications play a role too. For both men and women, having a spouse with gout raised the risk approximately 1.65 times, compared with someone in the general population.

The study also found gender differences in the relative contribution of each risk component. Heritability (genetic factors) was responsible for 35 percent of a man’s risk, but only 17 percent of a woman’s risk. Common environmental factors were responsible for 28 percent of a man’s risk and 18.5 percent of a woman’s risk. The rest of a person’s risk is made up of non-shared, environmental factors.

Dr. Kuo says researchers do not have an explanation for the gender differences they found. It may be biological; gout is known to be significantly more common in men than women, and women tend to develop it later in life. One explanation is that the female hormone estrogen enhances the excretion of uric acid by the kidney. But lifestyle choices also tend to vary by gender. For example, women in Taiwan typically consume fewer calories and less alcohol than men, he says, and certain foods and alcohol have been linked to the development of gout.

Dr. Kuo hopes his study’s findings will lead to research looking for susceptibility genes for gout (the study points out that few genes have been found so far) as well as more epidemiologic studies in other countries to identify shared environmental factors within families that contribute to the disease. He believes his results likely hold true for people in other countries and cultures, not just the Taiwanese, he says.

Scott Zashin, MD, a rheumatologist in Dallas, agrees. “It’s something I always assumed was the case, but it’s an important study in that it helps people remember there is a family link,” he says.

Based on the results of this study, Dr. Zashin says, people with a family history of gout may want to consider regularly getting their uric acid levels checked and adjusting their lifestyle, if the results come back high.

“If your uric acid is high, you might cut back on some things that might make you develop gout,” he explains. “Gout is the one type of arthritis where there is definite evidence that watching your diet and having one that’s low in foods with high uric acid content can decrease your risk of developing gout.”

A new study shows for the first time on a large scale that gout does indeed run in families. The study, published recently online in the journal Annals of the Rheumatic Diseases, also shows gender differences in gout risk from the impact of genetic and environmental factors.

“The composition of risk is different in men and women, but both genders are at higher risk if they have family history [of the disease],” explains the study’s lead author Chang-Fu Kuo, a PhD candidate at the University of Nottingham in the United Kingdom and a practicing rheumatologist in Taiwan. “And genes determine part of the risk but environmental factors shared by families – like diet habits – determine much more.”

Gout is a type of inflammatory arthritis that results from high levels of uric acid in the blood, or hyperuricemia. This can result in needle-like urate crystals accumulating in and around joints. Gout attacks (flares) cause sudden, severe pain, swelling and tenderness, usually in one joint – typically the joint of the big toe, although it less frequently affects some other joint in the foot, ankle, knee, hand, wrist or elbow. In more advance disease, it can affect multiple joints and sometimes the soft tissue and tendons.

Dr. Kuo says gout has long been observed to cluster in families, but previous evidence for a family link came mostly from small case series or case reports, not population-based studies. So he and his team of researchers sought to confirm the familial connection on a larger scale.

His study, conducted in Taiwan, which has one of the highest estimated rates of gout in the world, relied on a health insurance database with information on nearly all residents of the country.

The researchers found that out of more than 22 million residents, approximately 1 million had physician-diagnosed gout.

Both men and women with a first-degree relative – a sibling, parent or offspring – with gout were nearly two times more likely than someone in the general population to develop the disease. Having a twin with gout raised a person’s risk eight-fold. This risk was what the researchers call “dose dependent,” meaning that with each additional first-degree relative with gout a person had, that person’s risk increased even more.

Men with a second-degree relative – a nephew, niece, uncle, aunt, grandparent or grandchild – with the condition were 1.25 times more likely than someone in the general population to develop gout, and women with a second-degree relative were 1.4 times more likely to develop it.

Part of this genetic risk is thought to be linked to genes that control “renal urate clearance” – the elimination of crystal-causing uric acid from the blood by the kidneys.

But it’s not all genetics; environment and lifestyle factors such as diet, alcohol consumption and the use of certain medications play a role too. For both men and women, having a spouse with gout raised the risk approximately 1.65 times, compared with someone in the general population.

The study also found gender differences in the relative contribution of each risk component. Heritability (genetic factors) was responsible for 35 percent of a man’s risk, but only 17 percent of a woman’s risk. Common environmental factors were responsible for 28 percent of a man’s risk and 18.5 percent of a woman’s risk. The rest of a person’s risk is made up of non-shared, environmental factors.

Dr. Kuo says researchers do not have an explanation for the gender differences they found. It may be biological; gout is known to be significantly more common in men than women, and women tend to develop it later in life. One explanation is that the female hormone estrogen enhances the excretion of uric acid by the kidney. But lifestyle choices also tend to vary by gender. For example, women in Taiwan typically consume fewer calories and less alcohol than men, he says, and certain foods and alcohol have been linked to the development of gout.

Dr. Kuo hopes his study’s findings will lead to research looking for susceptibility genes for gout (the study points out that few genes have been found so far) as well as more epidemiologic studies in other countries to identify shared environmental factors within families that contribute to the disease. He believes his results likely hold true for people in other countries and cultures, not just the Taiwanese, he says.

Scott Zashin, MD, a rheumatologist in Dallas, agrees. “It’s something I always assumed was the case, but it’s an important study in that it helps people remember there is a family link,” he says.

Based on the results of this study, Dr. Zashin says, people with a family history of gout may want to consider regularly getting their uric acid levels checked and adjusting their lifestyle, if the results come back high.

“If your uric acid is high, you might cut back on some things that might make you develop gout,” he explains. “Gout is the one type of arthritis where there is definite evidence that watching your diet and having one that’s low in foods with high uric acid content can decrease your risk of developing gout.”